JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schwinger, R. H. G.
Right arrow Articles by Erdmann, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schwinger, R. H. G.
Right arrow Articles by Erdmann, E.

Vol. 283, Issue 1, 286-292, 1997

Effect of Cyclopiazonic Acid on the Force-Frequency Relationship in Human Nonfailing  Myocardium1

Robert H. G. Schwinger, Klara Brixius, Udo Bavendiek, Susanne Hoischen, Jochen Müller-Ehmsen, Birgit Bölck and Erland Erdmann

Klinik III für Innere Medizin der Universität zu Köln, 50924 Köln, Germany

The present study investigated the functional role of the sarcoplasmic reticulum Ca++-ATPase in contraction and relaxation, intracellular Ca++-transients, as well as on the force-frequency relationship in human myocardium. The Ca++-ATPase activity of membrane vesicles isolated from sarcoplasmic reticulum (SR) obtained from nonfailing donor hearts (n = 7) was measured in the presence of cyclopiazonic acid (CPA, 0-30 µM), a highly specific inhibitor of the Ca++-ATPase of the SR (SERCA). The effects of CPA on parameters of contraction and relaxation, force-frequency relationship and [Ca++]i transients (with fura-2) were studied on isolated left ventricular muscle strips from human nonfailing myocardium. CPA concentration-dependently inhibited SERCA activity of isolated SR vesicles. In the presence of CPA (30 µM) the former positive force-frequency relationship in human left ventricular nonfailing myocardium became negative. Especially at high frequencies of stimulation, CPA decreased developed tension, peak rate of tension rise and systolic fura-2-light emission, whereas time to peak tension, time to peak [Ca++]i, time to 95% relaxation, diastolic tension and diastolic Ca++ levels were increased. Peak rate of tension decay and time to half-relaxation and half-decay of [Ca++]i were not altered significantly after treatment with CPA. These findings provide evidence that the SERCA plays a functional role in the frequency-dependent increase in force of contraction in human myocardium. Because an impaired function of the SERCA is predominantly followed by alterations of inotropic and to a lesser degree of lusitropic function, other important factors to lower [Ca++]i and influence relaxation may be present in human myocardium to compensate for the reduced SERCA activity, e.g., Na+-Ca++ exchanger.

Copyright © by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Exp PhysiolHome page
N. S. Ghais, Y. Zhang, A. A. Grace, and C. L.-H. Huang
Arrhythmogenic actions of the Ca2+ channel agonist FPL-64716 in Langendorff-perfused murine hearts
Exp Physiol, February 1, 2009; 94(2): 240 - 254.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
D. M. Kaye, A. Preovolos, T. Marshall, M. Byrne, M. Hoshijima, R. Hajjar, J. A. Mariani, S. Pepe, K. R. Chien, and J. M. Power
Percutaneous Cardiac Recirculation-Mediated Gene Transfer of an Inhibitory Phospholamban Peptide Reverses Advanced Heart Failure in Large Animals
J. Am. Coll. Cardiol., July 17, 2007; 50(3): 253 - 260.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
F. Pillekamp, M. Reppel, O. Rubenchyk, K. Pfannkuche, M. Matzkies, W. Bloch, N. Sreeram, K. Brockmeier, and J. Hescheler
Force Measurements of Human Embryonic Stem Cell-Derived Cardiomyocytes in an In Vitro Transplantation Model
Stem Cells, January 1, 2007; 25(1): 174 - 180.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
D. G Taylor, L. D Parilak, M. M LeWinter, and H. J Knot
Quantification of the rat left ventricle force and Ca2+-frequency relationships: similarities to dog and human
Cardiovasc Res, January 1, 2004; 61(1): 77 - 86.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
K. F Frank, B. Bolck, E. Erdmann, and R. H.G Schwinger
Sarcoplasmic reticulum Ca2+-ATPase modulates cardiac contraction and relaxation
Cardiovasc Res, January 1, 2003; 57(1): 20 - 27.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
K. Brixius, S. Reicke, and R. H. G. Schwinger
Beneficial effects of the Ca2+ sensitizer levosimendan in human myocardium
Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H131 - H137.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. Herr, N. Smyth, S. Ullrich, F. Yun, P. Sasse, J. Hescheler, B. Fleischmann, K. Lasek, K. Brixius, R. H. G. Schwinger, et al.
Loss of Annexin A7 Leads to Alterations in Frequency-Induced Shortening of Isolated Murine Cardiomyocytes
Mol. Cell. Biol., July 1, 2001; 21(13): 4119 - 4128.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1997 by the American Society for Pharmacology and Experimental Therapeutics.